Self-protection of individual CD4+ T cells against R5 HIV-1 infection by the synthesis of anti-viral CCR5 ligands.
It is well established that paracrine secretion of anti-viral CCR5 ligands by CD8+ and CD4+ T cells can block the infection of activated CD4+ T cells by R5 and dual-tropic isolates of HIV-1. By contrast, because CD4+ T cells can be infected by HIV-1 and at least some subsets secrete anti-viral CCR5 ligands, it is possible that these ligands protect against HIV-1 via autocrine as well as paracrine pathways. Here we use a model primary CD4+ T cell response in vitro to show that individual CD4+ T cells that secrete anti-viral CCR5 ligands are 'self-protected' against infection with R5 but not X4 strains of HIV-1. This protection is selective for CD4+ T cells that secrete anti-viral CCR5 ligands in that activated CD4+ T cells in the same cultures remain infectable with R5 HIV-1. These data are most consistent with an autocrine pathway of protection in this system and indicate a previously unappreciated selective pressure on the emergence of viral variants and CD4+ T cell phenotypes during HIV-1 infection.
Guan
Yongjun
Y
Division of Basic Science and Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Abdelwahab
Sayed
S
Kamin-Lewis
Roberta
R
DeVico
Anthony L
AL
Lewis
George K
GK
D019898:Autocrine Communication; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007109:Immunity; D008024:Ligands; D019899:Paracrine Communication; D019713:Receptors, CCR5 / Q000378:metabolism*; D012641:Selection, Genetic; D013045:Species Specificity
D008024:Ligands; D019713:Receptors, CCR5